This resubmission proposes a study for testing the efficacy of remoxipride a putative atypical antipsychotic drug for efficacy in neuroleptic treatment resistant schizophrenic patients. It will also provide support for a significant public and academic liaison initiative; the Treatment Resistant Unit of the University of Maryland at Baltimore. We propose that it will also lead to the development of a standard clinical protocol to test other candidate atypical drugs in the future. The drugs will be tested in a drug-drug double-blind parallel group design versus chlorpromazine, with clozapine used at the study end to describe the response level of the study population. Patients will be selected for poor neuroleptic response with a history of at least one year of persistent symptoms accompanied by failure to respond to at least three adequate trials of neuroleptics. Patients who enter the 12-week remoxipride trial will also have failed to respond to six weeks of haloperidol therapy on our study unit. Remoxipride is a potent D2 dopamine receptor blocking agent which has a low in vivo affinity for the D2 receptor, similar to clozapine. Future candidate drugs will be selected based on the outcome of the first rial and will be the subject of future submissions. This design provides substantial power for testing the remoxipride superiority hypothesis. Results will be analyzed with regard to improvement in total BPRS score and psychotic symptoms. Negative symptoms and side effect changes will be assessed. This study size is based on a predicted effect of 11% difference in total symptoms and a 22% difference in positive symptoms with a power of 0.80 and alpha of 0.05 (two-tailed).